Prostaglandin E2 (PGE2) is secreted in high concentrations by a variety of tumors, including the murine Lewis lung carcinoma (LLC). The goal of this study is to determine if nonmetastatic LLC cells, by producing PGE2, could stimulate dissemination by metastatic LLC cells. The rationale for this study is based on our previous observations: (i) cloned nonmetastatic LLC cells secreted higher amounts of PGE2 than did cloned metastatic LLC cells, and (ii) in an in vitro migration model for tumor dissemination, exogenous PGE2 stimulated the migration of metastatic LLC cells but did not stimulate the migration of the nonmetastatic LLC cells. The role of tumor-derived PGE2 in promoting tumor dissemination will be further assessed in this proposed study. First, the in vitro model for tumor dissemination will be used to determine if PGE2- producing nonmetastatic LLC cells can stimulate the in vitro migration of the metastatic LLC cells. Second, in vivo studies will determine if PGE2-producing nonmetastatic LLC cells can stimulate dissemination and metastasis of the metastatic LLC cells. If migration or dissemination is stimulated, studies will determine if this is mediated by tumor-derived PGE2. The final portion of this proposed study will be to determine if the increased capacity of the metastatic LLC to migrate in the presence of PGE2 is correlated with an increased capacity to bind PGE2 and, in turn, to generate a cyclic adenosine 3',5'- monophosphate (cAMP) response. The results of this study may suggest that within a tumor mass, there are subpopulations of tumor cells which, by producing PGE2, can directly influence the capacity of other subpopulations of tumor cells to disseminate and to produce metastases.